Genome analysis helps in breeding more robust cows

Genome analysis of 234 bulls has put researchers, including several from Wageningen Livestock Research, on the trail of DNA variants which influence particular characteristics in breeding bulls. For example, two variants have proven responsible for disruptions to the development of embryos and for curly hair, which is disadvantageous because more ticks and parasites occur in curly hair than in short, straight hair. These are the first results of the large 1000 Bull Genomes project on which some 30 international researchers are collaborating. They report on their research in the most recent edition of the science journal Nature Genetics.Most breeding characteristics are influenced by not one but a multiplicity of variants. It is therefore important to be able to use all the variants in breeding, say the Wageningen researchers. In order to make this possible, Rianne van Binsbergen, PhD researcher at the Animal Breeding and Genomics Centre of Wageningen UR, investigated whether the genomes of all the common bulls in the Netherlands can be filled with the help of these 234 bulls. Currently, these bulls have been genotyped with markers of 50,000 or 700,000 DNA variants. The positive results indicate the direction for further research into the practical use of genome information in breeding.Dairy and beef cattle The project demonstrates how useful large-scale DNA analyses can be, says Professor Roel Veerkamp, Professor of Numerical Genetics at Wageningen University and board member of the 1000 Bull Genomes project. He emphasises that the requirements for dairy and beef cattle are becoming ever more exacting: “Until the mid nineties, a cow primarily had to produce a lot of milk. But since then, expectations have gone up. …

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Tuberculosis genomes recovered from 200-year-old Hungarian mummy

July 19, 2013 — Researchers at the University of Warwick have recovered tuberculosis (TB) genomes from the lung tissue of a 215-year old mummy using a technique known as metagenomics.The team, led by Professor Mark Pallen, Professor of Microbial Genomics at Warwick Medical School, working with Helen Donoghue at University College London and collaborators in Birmingham and Budapest, sought to use the technique to identify TB DNA in a historical specimen.The term ‘metagenomics’ is used to describe the open-ended sequencing of DNA from samples without the need for culture or target-specific amplification or enrichment. This approach avoids the complex and unreliable workflows associated with culture of bacteria or amplification of DNA and draws on the remarkable throughput and ease of use of modern sequencing approaches.The sample came from a Hungarian woman, Terézia Hausmann, who died aged 28 on 25 December 1797. Her mummified remains were recovered from a crypt in the town of Vác, Hungary. When the crypt was opened in 1994, it was found to contain the naturally mummified bodies of 242 people. Molecular analyses of the chest sample in a previous study confirmed the diagnosis of tuberculosis and hinted that TB DNA was extremely well preserved in her body.Professor Pallen explained the importance of the breakthrough, “Most other attempts to recover DNA sequences from historical or ancient samples have suffered from the risk of contamination, because they rely on amplification of DNA in the laboratory, plus they have required onerous optimisation of target-specific assays. The beauty of metagenomics is that it provides a simple but highly informative, assumption-free, one-size-fits-all approach that works in a wide variety of contexts. A few months ago we showed that metagenomics allowed us to identify an E. coli outbreak strains from faecal samples and a few weeks ago a similar approach was shown by another group to deliver a leprosy genome from historical material.”The research, published this week in the New England Journal of Medicine, showed that Terézia Hausmann suffered from a mixed infection with two different strains of the TB bacterium. This information, combined with work on contemporary tuberculosis, highlights the significance of mixed-strain infections, particularly when tuberculosis is highly prevalent.Professor Pallen added, “It was fascinating to see the similarities between the TB genome sequences we recovered and the genome of a recent outbreak strain in Germany. It shows once more that using metagenomics can be remarkably effective in tracking the evolution and spread of microbes without the need for culture — in this case, metagenomes revealed that some strain lineages have been circulating in Europe for more than two centuries.”

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New insight into the human genome through the lens of evolution

July 11, 2013 — By comparing the human genome to the genomes of 34 other mammals, Australian scientists have described an unexpectedly high proportion of functional elements conserved through evolution.Less than 1.5% of the human genome is devoted to conventional genes, that is, encodes for proteins. The rest has been considered to be largely junk. However, while other studies have shown that around 5-8% of the genome is conserved at the level of DNA sequence, indicating that it is functional, the new study shows that in addition much more, possibly up to 30%, is also conserved at the level of RNA structure.DNA is a biological blueprint that must be copied into another form before it can be actualised. Through a process known as ‘transcription’, DNA is copied into RNA, some of which ‘encodes’ the proteins that carry out the biological tasks within our cells. Most RNA molecules do not code for protein, but instead perform regulatory functions, such as determining the ways in which genes are expressed.Like infinitesimally small Lego blocks, the nucleic acids that make up RNA connect to each other in very specific ways, which force RNA molecules to twist and loop into a variety of complicated 3D structures.Dr Martin Smith and Professor John Mattick, from Sydney’s Garvan Institute of Medical Research, devised a method for predicting these complex RNA structures — more accurate than those used in the past — and applied it to the genomes of 35 different mammals, including bats, mice, pigs, cows, dolphins and humans. At the same time, they matched mutations found in the genomes with consistent RNA structures, inferring conserved function. Their findings are published in Nucleic Acids Research, now online.”Genomes accumulate mutations over time, some of which don’t change the structure of associated RNAs. If the sequence changes during evolution, yet the RNA structure stays the same, then the principles of natural selection suggest that the structure is functional and is required for the organism,” explained Dr Martin Smith.”Our hypothesis is that structures conserved in RNA are like a common template for regulating gene expression in mammals — and that this could even be extrapolated to vertebrates and less complex organisms.””We believe that RNA structures probably operate in a similar way to proteins, which are composed of structural domains that assemble together to give the protein a function.””We suspect that many RNA structures recruit specific molecules, such as proteins or other RNAs, helping these recruited elements to bond with each other. That’s the general hypothesis at the moment — that non-coding RNAs serve as scaffolds, tethering various complexes together, especially those that control genome organization and expression during development.””We know that many RNA transcripts are associated with diseases and developmental conditions, and that they are differentially expressed in distinct cells.””Our structural predictions can serve as an annotative tool to help researchers understand the function of these RNA transcripts.””That is the first step — the next is to describe the structures in more detail, figure out exactly what they do in the cell, then work out how they relate to our normal development and to disease.”

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